Experiments are proposed to study the effects of acute and chronic administration of alcohol, as well as withdrawal from chronic alcohol exposure, on neurotransmission in the noradrenergic-locus coeruleus (NE-LC) system. Recordings from single NE-LC neurons in anesthetized rats will examine the effects of various alcohol manipulations on the fiber conduction velocity, soma excitability, responsiveness to noxious sensory stimuli, and post-excitation inhibition of these cells. Similar records in unanesthetized behaving rats will determine the effects of these alcohol treatments on the responsiveness of NE-LC neurons to non-noxious sensory stimuli, as well as their spontaneous discharge during naturally occurring behaviors. Electrical stimulation of locus coeruleus, or iontophoresis of norepinephrine, will be used to test the effects of these same alcohol treatments on the postsynaptic responsiveness of cells in the cerebrocortex to activity in the NE-LC system. The long-term objectives of this research are to determine the effects of alcohol exposure on neurotransmission in the NE-LC system by examining changes induced in both pre- and postsynaptic elements. Such data will be valuable additions to the present sparse knowledge of the effects of alcohol on the physiology of this pervasive brain system. These experiments may provide insights into mechanisms involved in alcohol intoxication, addiction and withdrawal phenomena, and further elucidate the role of the NE-LC system in addiction in general.